3-hydroxy-3-methylbutyric acid (also referred to as beta-hydroxyisovalerate or HIV; see FIG. 1) is a metabolite of the essential amino acid leucine and is synthesized in the human body. It can be found in small quantities in grapefruit, alfalfa and catfish. It is also known to occur in some metabolic disorders of leucine catabolism, i.e. hypovaleric acidemia. It has been shown that 3-hydroxy-3-methylbutyric acid may have an effect on increasing muscle weight and strength (Nissen et al., J. Appl. Physiol. 81 (1996), 2095-2104). Wilson et al. (Nutrition & Metabolism 5 (2008)) proposes as the mechanisms of action the following:                increased sarcolemmal integrity via conversion by HMG CoA reductase        enhanced protein synthesis via the mTOR pathway        depression of protein degradation through inhibition of the ubiquitin pathway.        
3-hydroxy-3-methylbutyric acid is supposed to help muscles combat protein breakdown, assist in muscle repair and support increased endurance. It has been described to help patients with chronic obstructive pulmonary disease in hospital intensive care units, muscle wasting associated with HIV and cancer and trauma victims with severe injuries. Thus, it is of commercial interest because of its use as a muscle enhancer for bodybuilding and as a medicament for avoiding muscle wasting. U.S. Pat. No. 7,026,507 describes a process for preparing solid formulations of sodium 3-hydroxy-3-methylbutyrate in which, in a first process step, 4,4-dimethyloxetan-2-one is reacted with aqueous sodium hydroxide to form a solution of sodium 3-hydroxy-3-methylbutyrate, and then, if appropriate after concentration, the solution is applied, in a further process step, to synthetic silica, and in which the resultant product is, if appropriate, dried.
It would be desirable to provide a process for the production of 3-hydroxy-3-methylbutyrate which would be independent of inorganic production steps and which could be effected in living organisms thereby being environmentally sound and inexpensive. In this context, Lee et al. (Appl. Environ. Microbiol. 63 (1997), 4191-4195) describes a method for the production of 3-hydroxy-3-methylbutyrate by converting 3-methylbutyric acid to 3-hydroxy-3-methylbutyric acid using the microorganism Galactomyces reessii. However, although this process allowed the production of 3-hydroxy-3-methylbutyrate there is still a need to provide alternative efficient and cost effective ways of producing 3-hydroxy-3-methylbutyrate in particular by biological processes.
The present invention meets this demand for an alternative process for the production of 3-hydroxy-3-methylbutyrate and provides a method which is based on biological resources and allows to produce 3-hydroxy-3-methylbutyrate in vitro or in vivo in a microorganism and other species.